The aetiology of multiple sclerosis (MS) is as yet poorly understood. Multiple mechanisms in different disease stages are responsible for immunopathology in MS. HLA Class II DR2b (DRB1*1501 β, DRA1*0101 α) is the strongest genetic risk factor for MS. Remnants of ancient retroviruses in the human genome, termed human endogenous retroviruses (HERV), and Epstein-Barr virus (EBV) infection are also associated with MS. In silico analyses of human endogenous retroviral envelope (HERV env) proteins and three myelin proteins that are principal targets of an autoimmune response in MS showed sequence similarities between potential TH epitopes within pairs of viral and myelin peptides predicted to bind HLA DR2b. This led to the proposal that such molecular mimicry may potentially trigger MS. HLA DR2b binding characteristics of previously identified peptides from the three myelin proteins and HERV env proteins as well as additional in silico predicted peptides from other encephalitogenic brain proteins and EBV proteins were studied to further investigate molecular mimicry. Peptides containing potential TH epitopes from the myelin oligodendrocyte glycoprotein and HERV env previously predicted to bind HLA DR2b as well as other pertinent potential HLA DR2b-restricted TH epitopes were confirmed to bind HLA DR2b molecules. Molecular modelling of HLA DR2b in complex with high affinity peptides derived from MOG and HERV env proteins showed that their binding could occur in a similar manner to a HLA DR2b-binding peptide containing a known TH epitope. A structurally related pair of peptides predicted to bind HLA DR2b from the EBV protein EBNA1 and β synuclein, a brain protein implicated in MS, were also shown to similarly bind HLA DR2b. The findings justify investigating CD4+ T cell responses to the identified peptides.

中文翻译：

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人类内源性逆转录病毒包膜，爱泼斯坦-巴尔病毒和脑蛋白中的HLA DR2b结合肽，在多发性硬化症的分子模拟环境中。

尚不清楚多发性硬化症（MS）的病因。MS的免疫病理学负责不同疾病阶段的多种机制。HLA II类DR2b（DRB1 * 1501β，DRA1 * 0101α）是MS的最强遗传危险因素。MS中还存在人类基因组中古代逆转录病毒的残留物，称为人内源性逆转录病毒（HERV）和爱泼斯坦-巴尔病毒（EBV）感染。在计算机上对人内源性逆转录病毒包膜（HERV env）蛋白和三种髓磷脂蛋白（是MS中自身免疫应答的主要靶标）进行的计算机分析表明，预计结合HLA DR2b的病毒和髓磷脂肽对中潜在的TH表位之间的序列相似性。这导致了这样的提议，即这种分子模仿可能会触发MS。研究了先前从三种髓磷脂蛋白和HERV env蛋白中鉴定出的肽的HLA DR2b结合特性，以及来自其他致脑性脑蛋白和EBV蛋白的其他计算机预测的肽，以进一步研究分子模拟。含有来自髓磷脂少突胶质细胞糖蛋白和HERV env的潜在TH抗原决定簇的肽，先前被预测会结合HLA DR2b以及其他相关的潜在HLA DR2b限制性TH抗原决定簇被证实可以结合HLA DR2b分子。与衍生自MOG和HERV env蛋白的高亲和力肽复合的HLA DR2b分子模型显示，它们的结合可能以与含有已知TH表位的HLA DR2b结合肽相似的方式发生。还显示了结构上相关的一对肽，该对肽预计会结合EBV蛋白EBNA1的HLA DR2b和β突触核蛋白（一种与MS有关的脑蛋白），也相似地结合HLA DR2b。这些发现证明了研究CD4 + T细胞对鉴定出的肽的反应是正确的。